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Comparative analysis of cancer genes in the human and chimpanzee genomes

Xose S Puente1 email, Gloria Velasco1 email, Ana Gutiérrez-Fernández1 email, Jaume Bertranpetit2 email, Mary-Claire King3 email and Carlos López-Otín1 email

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain

Unitat de Biologia Evolutiva, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

Departments of Medicine and Genome Sciences, School of Medicine, University of Washington, Seattle WA-98195, USA

author email corresponding author email

BMC Genomics 2006, 7:15doi:10.1186/1471-2164-7-15

Published: 26 January 2006

Abstract

Background

Cancer is a major medical problem in modern societies. However, the incidence of this disease in non-human primates is very low. To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes.

Results

This analysis has revealed that all examined human cancer genes are present in chimpanzee, contain intact open reading frames and show a high degree of conservation between both species. However, detailed analysis of this set of genes has shown some differences in genes of special relevance for human cancer. Thus, the chimpanzee gene encoding p53 contains a Pro residue at codon 72, while this codon is polymorphic in humans and can code for Arg or Pro, generating isoforms with different ability to induce apoptosis or interact with p73. Moreover, sequencing of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that prematurely truncates the co-regulated NBR2 gene.

Conclusion

These data suggest that small differences in cancer genes, as those found in tumor suppressor genes, might influence the differences in cancer susceptibility between human and chimpanzee. Nevertheless, further analysis will be required to determine the exact contribution of the genetic changes identified in this study to the different cancer incidence in non-human primates.


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